Yamada Risa, Harigai Masayoshi, Katsumata Yasuhiro
Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Int J Rheum Dis. 2025 Jul;28(7):e70353. doi: 10.1111/1756-185X.70353.
We retrospectively compared the outcomes of protocolized tacrolimus-based and non-protocolized ciclosporin-based triple-combination therapies in consecutive patients with newly diagnosed interstitial lung disease (ILD) and antimelanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM).
Clinical data from consecutive adult patients with newly diagnosed anti-MDA5-positive DM-associated ILD in our hospital from 2013 to 2022 were analyzed. Recent cases received protocolized therapy with high-dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IVCY). Earlier cases received non-protocolized ciclosporin-based triple-combination therapy. The observation period was 12 months. The outcomes included a composite of death or requirement for long-term domiciliary oxygen therapy (LTOT), mortality, GC and IVCY doses, and cytomegalovirus reactivation rates within 12 months.
Protocolized therapy with tacrolimus (n = 14) and non-protocolized therapy with ciclosporin (n = 10) groups had similar baseline characteristics. No deaths or LTOT were observed in the protocolized therapy with the tacrolimus group, whereas four patients in the non-protocolized therapy with ciclosporin group experienced these outcomes (difference, 40 percentage points; 95% CI, 10 to 70; p = 0.020). The 12-month mortality rates were not significantly different between the two groups (p = 0.16). The protocolized therapy with the tacrolimus group had lower GC dosages at 6 months, more total cycles and cumulative doses of IVCY, and lower cytomegalovirus reactivation rates than the non-protocolized therapy with the ciclosporin group (p < 0.05).
Protocolized tacrolimus-based triple-combination therapy demonstrated better outcomes than non-protocolized ciclosporin-based triple-combination therapy in patients with anti-MDA5-positive DM-associated ILD. Reduced GC doses and more intensive IVCY use also presumably contributed to better outcomes in the protocolized therapy with the tacrolimus group.
我们回顾性比较了在新诊断的间质性肺病（ILD）和抗黑色素瘤分化相关基因5（MDA5）阳性皮肌炎（DM）的连续患者中，基于他克莫司的标准化方案和基于环孢素的非标准化三联组合疗法的疗效。
分析了2013年至2022年我院连续诊断为抗MDA5阳性DM相关ILD的成年患者的临床数据。近期病例接受了高剂量糖皮质激素（GCs）、他克莫司和静脉注射环磷酰胺（IVCY）的标准化治疗。早期病例接受了基于环孢素的非标准化三联组合疗法。观察期为12个月。结局指标包括死亡或需要长期家庭氧疗（LTOT）的复合指标、死亡率、GC和IVCY剂量，以及12个月内的巨细胞病毒再激活率。
基于他克莫司的标准化治疗组（n = 14）和基于环孢素的非标准化治疗组（n = 10）具有相似的基线特征。基于他克莫司的标准化治疗组未观察到死亡或LTOT情况，而基于环孢素的非标准化治疗组有4例患者出现了这些结局（差异为40个百分点；95%CI，10至70；p = 0.020）。两组的12个月死亡率无显著差异（p = 0.16）。与基于环孢素的非标准化治疗组相比，基于他克莫司的标准化治疗组在6个月时GC剂量更低，IVCY的总疗程和累积剂量更多，巨细胞病毒再激活率更低（p < 0.05）。
在抗MDA5阳性DM相关ILD患者中，基于他克莫司的标准化三联组合疗法比基于环孢素的非标准化三联组合疗法显示出更好的疗效。GC剂量的减少和IVCY更强化的使用可能也是基于他克莫司的标准化治疗组疗效更好的原因。
